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Search Results (743)

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29 pages, 14681 KiB  
Article
Single-Nucleus RNA Sequencing and Spatial Transcriptomics Reveal Cellular Heterogeneity and Intercellular Communication Networks in the Hypothalamus–Pituitary–Ovarian Axis of Pregnant Mongolian Cattle
by Yanchun Bao, Fengying Ma, Chenxi Huo, Hongxia Jia, Yunhan Li, Xiaoyi Yang, Jiajing Liu, Pengbo Gu, Caixia Shi, Mingjuan Gu, Lin Zhu, Yu Wang, Bin Liu, Risu Na and Wenguang Zhang
Animals 2025, 15(15), 2277; https://doi.org/10.3390/ani15152277 - 4 Aug 2025
Viewed by 101
Abstract
The hypothalamus–pituitary–ovarian (HPO) axis orchestrates reproductive functions through intricate neuroendocrine crosstalk. Here, we integrated single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (ST) to decode the cellular heterogeneity and intercellular communication networks in the reproductive systems of pregnant Mongolian cattle. We retained a total [...] Read more.
The hypothalamus–pituitary–ovarian (HPO) axis orchestrates reproductive functions through intricate neuroendocrine crosstalk. Here, we integrated single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (ST) to decode the cellular heterogeneity and intercellular communication networks in the reproductive systems of pregnant Mongolian cattle. We retained a total of 6161 high-quality nuclei from the hypothalamus, 14,715 nuclei from the pituitary, and 26,072 nuclei from the ovary, providing a comprehensive cellular atlas across the HPO axis. In the hypothalamus, neurons exhibited synaptic and neuroendocrine specialization, with glutamatergic subtype Glut4 serving as a TGFβ signaling hub to regulate pituitary feedback, while GABAergic GABA1 dominated PRL signaling, likely adapting maternal behavior. Pituitary stem cells dynamically replenished endocrine populations via TGFβ, and lactotrophs formed a PRLPRLR paracrine network with stem cells, synergizing mammary development. Ovarian luteal cells exhibited steroidogenic specialization and microenvironmental synergy: endothelial cells coregulated TGFβ-driven angiogenesis and immune tolerance, while luteal–stromal PRLPRLR interactions amplified progesterone synthesis and nutrient support. Granulosa cells (GCs) displayed spatial-functional stratification, with steroidogenic GCs persisting across pseudotime as luteinization precursors, while atretic GCs underwent apoptosis. Spatial mapping revealed GCs’ annular follicular distribution, mediating oocyte–somatic crosstalk, and luteal–endothelial colocalization supporting vascularization. This study unveils pregnancy-specific HPO axis regulation, emphasizing multi-organ crosstalk through TGFβ/PRL pathways and stem cell-driven plasticity, offering insights into reproductive homeostasis and pathologies. Full article
(This article belongs to the Section Cattle)
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11 pages, 3222 KiB  
Article
Cervical Ectopic Pregnancies—Imaging and Endovascular Treatment
by Maciej Szmygin, Bartosz Kłobuszewski, Karolina Nieoczym, Weronika Dymara-Konopka, Sławomir Woźniak, Hanna Szmygin, Łukasz Światłowski and Krzysztof Pyra
Diagnostics 2025, 15(15), 1956; https://doi.org/10.3390/diagnostics15151956 - 4 Aug 2025
Viewed by 93
Abstract
Objective: Cervical pregnancy (CP) accounts for less than 1% of all ectopic pregnancies. The standard of management for CP is still under detailed investigation; however, among the known treatment methods, super-selective uterine artery embolization (UAE) and the use of methotrexate (MTX) have [...] Read more.
Objective: Cervical pregnancy (CP) accounts for less than 1% of all ectopic pregnancies. The standard of management for CP is still under detailed investigation; however, among the known treatment methods, super-selective uterine artery embolization (UAE) and the use of methotrexate (MTX) have emerged as effective and minimally invasive options in recent years. Our aim is to present our center’s experience and provide available evidence evaluating the efficacy of UAE in the treatment of CP. Materials and Methods: This single-center and retrospective study evaluated the procedural and clinical outcomes of patients with CP who underwent endovascular uterine embolization with MTX between 2017 and 2024. Both procedural and clinical efficacy and safety, as well as the rate of complications and long-term outcomes, were noted. Results: A total of nine patients were diagnosed with CP (imaging examination included transvaginal ultrasound and/or magnetic resonance imaging) and referred for endovascular treatment. The mean age of the patients was 36.7 years, and the mean gestational age on admission was 9 weeks. In all cases, selective catheterization of supplying vessels and subsequent embolization with a mixture of methotrexate and gel sponge was carried out. The technical success rate was 100% with no complications. Follow-up ultrasound confirmed the disappearance of the flow signal around the intracervical gestational sac in all cases. Conclusions: In conclusion, this retrospective study demonstrated the procedural and clinical safety and efficacy of uterine artery embolization in patients with cervical pregnancy. This is why endovascular therapy should be proposed to these individuals and be included in treatment options discussed during multidisciplinary boards. Full article
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3 pages, 468 KiB  
Interesting Images
Fatal Congenital Heart Disease in a Postpartum Woman
by Corina Cinezan, Camelia Bianca Rus, Mihaela Mirela Muresan and Ovidiu Laurean Pop
Diagnostics 2025, 15(15), 1952; https://doi.org/10.3390/diagnostics15151952 - 4 Aug 2025
Viewed by 115
Abstract
The image represents the post-mortem heart of a 28-year-old female patient, diagnosed in childhood with complete common atrioventricular canal defect. At time of diagnosis, the family refused surgery, as did the patient during her adulthood. Despite being advised against pregnancy, she became pregnant. [...] Read more.
The image represents the post-mortem heart of a 28-year-old female patient, diagnosed in childhood with complete common atrioventricular canal defect. At time of diagnosis, the family refused surgery, as did the patient during her adulthood. Despite being advised against pregnancy, she became pregnant. On presentation to hospital, she was cyanotic, with clubbed fingers, and hemodynamically unstable, in sinus rhythm, with Eisenmenger syndrome and respiratory failure partially responsive to oxygen. During pregnancy, owing to systemic vasodilatation, the right-to-left shunt is increased, with more severe cyanosis and low cardiac output. Echocardiography revealed the complete common atrioventricular canal defect, with a single atrioventricular valve with severe regurgitation, right ventricular hypertrophy, pulmonary artery dilatation, severe pulmonary hypertension and a hypoplastic left ventricle. The gestational age at delivery was 38 weeks. She gave birth to a healthy boy, with an Apgar score of 10. The vaginal delivery was chosen by an interdisciplinary team. The cesarean delivery and the anesthesia were considered too risky compared to vaginal delivery. Three days later, the patient died. The autopsy revealed hepatomegaly, a greatly hypertrophied right ventricle with a purplish clot ascending the dilated pulmonary arteries and a hypoplastic left ventricle with a narrowed chamber. A single valve was observed between the atria and ventricles, making all four heart chambers communicate, also insufficiently developed interventricular septum and its congenital absence in the cranial third. These morphological changes indicate the complete common atrioventricular canal defect, with right ventricular dominance, which is a rare and impressive malformation that requires mandatory treatment in early childhood in order for the condition to be solved. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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19 pages, 1016 KiB  
Article
Genetic Associations of ITGB3, FGG, GP1BA, PECAM1, and PEAR1 Polymorphisms and the Platelet Activation Pathway with Recurrent Pregnancy Loss in the Korean Population
by Eun Ju Ko, Eun Hee Ahn, Hyeon Woo Park, Jae Hyun Lee, Da Hwan Kim, Young Ran Kim, Ji Hyang Kim and Nam Keun Kim
Int. J. Mol. Sci. 2025, 26(15), 7505; https://doi.org/10.3390/ijms26157505 - 3 Aug 2025
Viewed by 239
Abstract
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women [...] Read more.
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article
(This article belongs to the Special Issue Molecular Research in Gynecological Diseases—2nd Edition)
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22 pages, 5939 KiB  
Article
Single-Nucleus Transcriptome Sequencing Unravels Physiological Differences in Holstein Cows Under Different Physiological States
by Peipei Li, Yaqiang Guo, Yanchun Bao, Caixia Shi, Lin Zhu, Mingjuan Gu, Risu Na and Wenguang Zhang
Genes 2025, 16(8), 931; https://doi.org/10.3390/genes16080931 - 3 Aug 2025
Viewed by 111
Abstract
Background: Against the backdrop of the large-scale and intensive development of the livestock industry, enhancing the reproductive efficiency of cattle has become a crucial factor in industrial development. Holstein cows, as the most predominant dairy cattle breed globally, are characterized by high milk [...] Read more.
Background: Against the backdrop of the large-scale and intensive development of the livestock industry, enhancing the reproductive efficiency of cattle has become a crucial factor in industrial development. Holstein cows, as the most predominant dairy cattle breed globally, are characterized by high milk yield and excellent milk quality. However, their reproductive efficiency is comprehensively influenced by a variety of complex factors, and improving their reproductive performance faces numerous challenges. The ovary, as the core organ of the female reproductive system, plays a decisive role in embryonic development and pregnancy maintenance. It is not only the site where eggs are produced and developed but it also regulates the cow’s estrous cycle, ovulation process, and the establishment and maintenance of pregnancy by secreting various hormones. The normal functioning of the ovary is crucial for the smooth development of the embryo and the successful maintenance of pregnancy. Methods: Currently, traditional sequencing technologies have obvious limitations in deciphering ovarian function and reproductive regulatory mechanisms. To overcome the bottlenecks of traditional sequencing technologies, this study selected Holstein cows as the research subjects. Ovarian samples were collected from one pregnant and one non-pregnant Holstein cow, and single-nucleus transcriptome sequencing technology was used to conduct an in-depth study on the ovarian cells of Holstein cows. Results: By constructing a cell type-specific molecular atlas of the ovaries, nine different cell types were successfully identified. This study compared the proportions of ovarian cell types under different physiological states and found that the proportion of endothelial cells decreased during pregnancy, while the proportions of granulosa cells and luteal cells increased significantly. In terms of functional enrichment analysis, oocytes during both pregnancy and non-pregnancy play roles in the “cell cycle” and “homologous recombination” pathways. However, non-pregnant oocytes are also involved in the “progesterone-mediated oocyte maturation” pathway. Luteal cells during pregnancy mainly function in the “cortisol synthesis and secretion” and “ovarian steroidogenesis” pathways; non-pregnant luteal cells are mainly enriched in pathway processes such as the “AMPK signaling pathway”, “pyrimidine metabolism”, and “nucleotide metabolism”. Cell communication analysis reveals that there are 51 signaling pathways involved in the pregnant ovary, with endothelial cells, granulosa cells, and luteal cells serving as the core communication hubs. In the non-pregnant ovary, there are 48 pathways, and the interaction between endothelial cells and stromal cells is the dominant mode. Conclusions: This study provides new insights into the regulatory mechanisms of reproductive efficiency in Holstein cows. The differences in the proportions of ovarian cell types, functional pathways, and cell communication patterns under different physiological states, especially the increase in the proportions of granulosa cells and luteal cells during pregnancy and the specificity of related functional pathways, indicate that these cells play a crucial role in the reproductive process of cows. These findings also highlight the importance of ovarian cells in pathways such as “cell cycle”, “homologous recombination”, and “progesterone-mediated oocyte maturation”, as well as the cell communication mechanisms in regulating ovarian function and reproductive performance. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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12 pages, 682 KiB  
Article
Structural Posterior Fossa Malformations: MR Imaging and Neurodevelopmental Outcome
by Jorden Halevy, Hadar Doitch Amdurski, Michal Gafner, Shalev Fried, Tomer Ziv-Baran and Eldad Katorza
Diagnostics 2025, 15(15), 1945; https://doi.org/10.3390/diagnostics15151945 - 3 Aug 2025
Viewed by 312
Abstract
Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed [...] Read more.
Objectives: The increasing use of fetal MRI has increased the diagnosis of posterior fossa malformations, yet the long-term neurodevelopmental outcomes of affected fetuses remain unclear. This study aims to examine the long-term neurodevelopmental outcomes of fetuses with structural posterior fossa malformation diagnosed on fetal MRI. Methods: A historical cohort study was conducted at a single tertiary referral center, including fetuses diagnosed with structural posterior fossa malformations and apparently healthy fetuses who underwent fetal brain MRI between 2011 and 2019. Maternal, pregnancy, and newborn characteristics were compared between groups, alongside long-term neurodevelopmental outcomes using the Vineland Adaptive Behavior Scales II (VABS-II) questionnaire. This included an extensive assessment of malformation types, additional structural, genetic, or neurodevelopmental anomalies, and outcomes. Results: A total of 126 fetuses met the inclusion criteria, of which 70 were apparently healthy fetuses, and 56 had structural posterior fossa malformations. Among the latter, 18 pregnancies were terminated, 4 resulted in neonatal death, and 11 were lost to follow-up. No significant differences were found in the overall neurodevelopmental outcomes between fetuses with structural posterior fossa malformation (93.4 ± 19.0) and apparently healthy fetuses (99.8 ± 13.8). Motor skills scores were lower among fetuses with structural posterior fossa malformations (87.7 ± 16.5 vs. 99.3 ± 17.2, p = 0.01) but remained within the normal range. Conclusion: Fetuses with structural posterior fossa malformations may exhibit normal long-term neurodevelopmental outcomes if no additional anomalies are detected during thorough prenatal screening that includes proper sonographic, biochemical and genetic screening, as well as fetal MRI. Further research with larger cohorts and longer-term assessments is recommended to validate these findings and support clinical decision-making. Full article
(This article belongs to the Special Issue Advances in Fetal Imaging)
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11 pages, 301 KiB  
Article
Impact of Maternal Overweight and Obesity on Pregnancy Outcomes Following Cesarean Delivery: A Retrospective Cohort Study
by Zlatina Nikolova, Milena Sandeva, Ekaterina Uchikova, Angelina Kirkova-Bogdanova, Daniela Taneva, Marieta Vladimirova and Lyubomira Georgieva
Healthcare 2025, 13(15), 1893; https://doi.org/10.3390/healthcare13151893 - 2 Aug 2025
Viewed by 238
Abstract
Background/Objectives: Maternal overweight and obesity are critical factors increasing the risk of various pregnancy complications. Maternal obesity can lead to fetal macrosomia and a heightened risk of intrauterine death, with long-term implications for the child’s health. This study aimed to analyze the [...] Read more.
Background/Objectives: Maternal overweight and obesity are critical factors increasing the risk of various pregnancy complications. Maternal obesity can lead to fetal macrosomia and a heightened risk of intrauterine death, with long-term implications for the child’s health. This study aimed to analyze the incidence of obesity and its impact on pregnancy outcomes in women who delivered by cesarean section at the University Hospital “St. George”, Plovdiv. Methods: A single-center retrospective cohort study was conducted. The documentary method was used for gathering data. Records were randomly selected. The statistical methods used included mean values, confidence intervals (of mean), frequency, and the Kolmogorov–Smirnov test for normality of distribution. Data comparisons were performed using the Mann–Whitney test. Mean values of numerical variables were compared using the independent samples t-test. Results: In total, 46.36% of women in this study were affected by obesity to varying degrees, and the proportion of women who were overweight at the end of their pregnancy was 37.85%. In the studied cohort, 15.99% of women were affected by hypertensive complications. This significant prevalence of obesity highlights concerns regarding body weight among women of reproductive age. This study emphasized a strong correlation between maternal obesity, particularly severe obesity, and the occurrence of preeclampsia. Conclusions: In this study among women who delivered by cesarean section, a significant proportion of them were affected by overweight and obesity. Data for our country are insufficient, and a more in-depth study of this problem is needed. Future research should explore the long-term impacts of maternal obesity on the health of the mother and the newborn. Full article
(This article belongs to the Special Issue Focus on Maternal, Pregnancy and Child Health)
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15 pages, 245 KiB  
Article
Exploring Single-Nucleotide Polymorphisms in Primary and Secondary Male Infertility
by Fatina W. Dahadhah, Mohanad Odeh, Heba A. Ali, Jihad A. M. Alzyoud and Manal Issam Abu Alarjah
Med. Sci. 2025, 13(3), 109; https://doi.org/10.3390/medsci13030109 - 1 Aug 2025
Viewed by 189
Abstract
Background/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive [...] Read more.
Background/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive a first child) and secondary male infertility (which occurs when a man who has already fathered a child faces difficulty conceiving again) remain poorly understood at the genetic level. This study explored the role of single-nucleotide polymorphisms (SNPs) in mitochondrial genes (MT-ND3, MT-ND4L, and MT-ND4) in primary and secondary male infertility. Methods: This study analyzed the genotype distributions of SNPs in 68 infertile males (49 with primary infertility and 19 with secondary infertility) using Sanger sequencing. Results: Key findings revealed that studied SNPs were significantly associated with infertility type. Specifically, rs2857285 (T>C,G) in the ND4 gene showed a significant correlation (p = 0.023) with the TT genotype, which is prominent in primary infertility. Another SNP, rs28358279 (T>A,C) in the ND4L gene, also demonstrated a significant correlation (p = 0.046) with the TT genotype, being more common in primary infertility. In addition, rs869096886 (A>G) in the ND4 gene had a borderline correlation (p = 0.051), indicating a possible association between this SNP and reproductive duration. Conclusions: This study emphasizes the potential relevance of mitochondrial malfunction in male infertility, specifically the effects of studied SNPs on sperm survival and function over time. These findings suggest that certain mitochondrial SNPs might be potential biomarkers for infertility risk. Larger studies are needed to confirm these associations and examine the functional effects of these SNPs. Combining genetic analysis with environmental and lifestyle factors could enhance our understanding of male infertility and improve diagnostic and therapeutic strategies. Full article
19 pages, 1584 KiB  
Article
Polymorphic Variants of Selected Genes Regulating Bile Acid Homeostasis in Women with Intrahepatic Cholestasis of Pregnancy
by Krzysztof Piątek, Grażyna Kurzawińska, Marcin Ożarowski, Piotr Józef Olbromski, Adam Kamiński, Maciej Brązert, Tomasz M. Karpiński, Wiesław Markwitz and Agnieszka Seremak-Mrozikiewicz
Int. J. Mol. Sci. 2025, 26(15), 7456; https://doi.org/10.3390/ijms26157456 - 1 Aug 2025
Viewed by 114
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is [...] Read more.
Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is to evaluate the association between CYP7A1, NR1H1, RXRA, and PPARA gene variants and risk of ICP. Five single nucleotide variants (SNVs), rs3808607 (CYP7A1), rs56163822 (NR1H4), rs1800206 (PPARA), rs749759, and rs11381416 (NR2B1), were genotyped in a group of 96 ICP and 211 controls. The T allele of the CYP7A1 (rs3808607) variant may be a protective factor against ICP risk (OR = 0.697, 95% CI: 0.495–0.981, p = 0.038). Genetic model analysis showed that rs3808607 was associated with decreased risk of ICP under dominant (OR = 0.55, 95% CI: 0.32–3.16, p = 0.032, AIC = 380.9) and log-additive models (OR = 0.71, 95% CI: 0.51–1.00, p = 0.046, AIC = 381.4). The A insertion in the rs11381416 NR2B1 variant was associated with the degree of elevation in the liver function tests TBA (34.3 vs. 18.8 μmol/L, p = 0.002), ALT (397.0 vs. 213.0 IU/L, p = 0.017), and AST (186.0 vs. 114.4 IU/L, p = 0.032) in ICP women. Results indicate an association between the CYP7A1 rs3808607 and the risk of ICP and the association of the rs11381416 of the NR2B1 receptor with higher values of liver function tests in women with ICP. A better understanding of the cooperation of proteins involved in BA metabolism may have important therapeutic implications in ICP and other hepatobiliary diseases. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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24 pages, 624 KiB  
Systematic Review
Integrating Artificial Intelligence into Perinatal Care Pathways: A Scoping Review of Reviews of Applications, Outcomes, and Equity
by Rabie Adel El Arab, Omayma Abdulaziz Al Moosa, Zahraa Albahrani, Israa Alkhalil, Joel Somerville and Fuad Abuadas
Nurs. Rep. 2025, 15(8), 281; https://doi.org/10.3390/nursrep15080281 - 31 Jul 2025
Viewed by 165
Abstract
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping [...] Read more.
Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article
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14 pages, 1694 KiB  
Article
The Role of MLPA in Detecting Syndromic Submicroscopic Copy Number Variations in Normal QF-PCR Miscarriage Specimens
by Gabriela Popescu-Hobeanu, Mihai-Gabriel Cucu, Alexandru Calotă-Dobrescu, Luminița Dragotă, Anca-Lelia Riza, Ioana Streață, Răzvan Mihail Pleșea, Ciprian Laurențiu Pătru, Cristina Maria Comănescu, Ștefania Tudorache, Dominic Iliescu and Florin Burada
Genes 2025, 16(8), 867; https://doi.org/10.3390/genes16080867 - 24 Jul 2025
Viewed by 332
Abstract
Background/Objectives: Miscarriage is an increasingly common event worldwide arising from various factors, and identifying its etiology is important for planning and managing any future pregnancies. It is estimated that about half of early pregnancy loss cases are caused by genetic abnormalities, while [...] Read more.
Background/Objectives: Miscarriage is an increasingly common event worldwide arising from various factors, and identifying its etiology is important for planning and managing any future pregnancies. It is estimated that about half of early pregnancy loss cases are caused by genetic abnormalities, while a significantly lower rate is found in late pregnancy loss. Multiplex ligation-dependent probe amplification (MLPA) can detect small changes within a gene with precise breakpoints at the level of a single exon. The aim of our study was to identify the rate of copy number variations (CNVs) in spontaneous pregnancy loss samples after having previously tested them via quantitative fluorescence PCR (QF-PCR), with no abnormal findings. Methods: DNA was extracted from product-of-conception tissue samples, followed by the use of an MLPA kit for the detection of 31 microdeletion/microduplication syndromes (SALSA® MLPA® Probemix P245 Microdeletion Syndromes-1A, MRC-Holland, Amsterdam, The Netherlands). Results: A total of 11 (13.1%) out of the 84 successfully tested samples showed CNVs. Duplications accounted for 9.5% of the analyzed samples (eight cases), while heterozygous or hemizygous deletions were present in three cases (3.6%). Among all the detected CNVs, only three were certainly pathogenic (3.6%), with two deletions associated with DiGeorge-2 syndrome and Rett syndrome, respectively, and a 2q23.1 microduplication syndrome, all detected in early pregnancy loss samples. For the remaining cases, additional genetic tests (e.g., aCGH/SNP microarray) are required to establish CNV size and gene content and therefore their pathogenicity. Conclusions: MLPA assays seem to have limited value in detecting supplementary chromosomal abnormalities in miscarriages. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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14 pages, 787 KiB  
Article
Preimplantation Genetic Testing for Aneuploidy Versus Morphological Selection in Women Aged 35–42: Results of a Pilot Randomized Controlled Trial
by Yusuf Beebeejaun, Daniela Bakalova, Anastasia Mania, Timothy Copeland, Ippokratis Sarris, Kypros Nicolaides, Antonio Capalbo and Sesh K. Sunkara
J. Clin. Med. 2025, 14(14), 5166; https://doi.org/10.3390/jcm14145166 - 21 Jul 2025
Viewed by 516
Abstract
Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women [...] Read more.
Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article
(This article belongs to the Special Issue Female Infertility: Clinical Diagnosis and Treatment)
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11 pages, 1218 KiB  
Article
Predictive Ability of an Objective and Time-Saving Blastocyst Scoring Model on Live Birth
by Bing-Xin Ma, Feng Zhou, Guang-Nian Zhao, Lei Jin and Bo Huang
Biomedicines 2025, 13(7), 1734; https://doi.org/10.3390/biomedicines13071734 - 15 Jul 2025
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Abstract
Objectives: With the development of artificial intelligence technology in medicine, an intelligent deep learning-based embryo scoring system (iDAScore) has been developed on full-time lapse sequences of embryos. It automatically ranks embryos according to the likelihood of achieving a fetal heartbeat with no manual [...] Read more.
Objectives: With the development of artificial intelligence technology in medicine, an intelligent deep learning-based embryo scoring system (iDAScore) has been developed on full-time lapse sequences of embryos. It automatically ranks embryos according to the likelihood of achieving a fetal heartbeat with no manual input from embryologists. To ensure its performance, external validation studies should be performed at multiple clinics. Methods: A total of 6291 single vitrified–thawed blastocyst transfer cycles from 2018 to 2021 at the Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed by the iDAScore model. Patients with two or more blastocysts transferred and blastocysts that were not cultured in a time-lapse incubator were excluded. Blastocysts were divided into four comparably sized groups by first sorting their iDAScore values in ascending order and then compared with the clinical, perinatal, and neonatal outcomes. Results: Our results showed that clinical pregnancy, miscarriage, and live birth significantly correlated with iDAScore (p < 0.001). For perinatal and neonatal outcomes, no significant difference was shown in four iDAScore groups, except sex ratio. Uni- and multivariable logistic regressions showed that iDAScore was significantly positively correlated with live birth rate (p < 0.05). Conclusions: In conclusion, the objective ranking can prioritize embryos reliably and rapidly for transfer, which could allow embryologists more time for processes requiring hands-on procedures. Full article
(This article belongs to the Special Issue The Art of ART (Assisted Reproductive Technologies))
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13 pages, 815 KiB  
Article
An Artificial Intelligence-Based Model to Predict Pregnancy After Intrauterine Insemination: A Retrospective Analysis of 9501 Cycles
by Jaume Minano Masip, Camille Grysole, Penelope Borduas, Isaac-Jacques Kadoch, Simon Phillips, Doina Precup and Daniel Dufort
J. Pers. Med. 2025, 15(7), 308; https://doi.org/10.3390/jpm15070308 - 12 Jul 2025
Viewed by 416
Abstract
Background/Objectives: Intrauterine insemination (IUI) is a common first-line approach in the treatment of numerous infertile couples, especially in cases of unexplained infertility. Its relatively low success rate, however, could benefit from the development of AI-based support tools to predict its outcome, thus helping [...] Read more.
Background/Objectives: Intrauterine insemination (IUI) is a common first-line approach in the treatment of numerous infertile couples, especially in cases of unexplained infertility. Its relatively low success rate, however, could benefit from the development of AI-based support tools to predict its outcome, thus helping the clinical management of patients undergoing IUI cycles. Our objective was to develop a robust and accurate machine learning model that predicts pregnancy outcomes following IUI. Methods: A retrospective, observational, and single-center study was conducted. In total, 3535 couples (aged 18–43 years) that underwent IUI between January 2011 and December 2015 were recruited. Twenty-one clinical and laboratory parameters of 9501 IUI cycles were used to train different machine learning algorithms. Accuracy of pregnancy outcome was evaluated by an area under the curve (AUC) analysis. Results: The linear SVM outperformed AdaBoost, Kernel SVM, Random Forest, Extreme Forest, Bagging, and Voting classifiers. Pre-wash sperm concentration, the ovarian stimulation protocol, cycle length, and maternal age were strong predictors of a positive pregnancy test following IUI (AUC = 0.78). Paternal age was found to be the worst predictor. Conclusions: Our Linear SVM model predicts a positive pregnancy outcome following IUI. Although this model shows value for the clinical management of infertile patients and informed decision-making by the patients, further validation using independent datasets is required prior to clinical implementation. Full article
(This article belongs to the Section Omics/Informatics)
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12 pages, 1450 KiB  
Article
Polyhydramnios at Term in Gestational Diabetes: Should We Be Concerned?
by Mercedes Horcas-Martín, Tania Luque-Patiño, Claudia Usandizaga-Prat, Elena Díaz-Fernández, Victoria Melero-Jiménez, Luis Vázquez-Fonseca, Francisco Visiedo, José Román Broullón-Molanes, Rocío Quintero-Prado and Fernando Bugatto
Children 2025, 12(7), 920; https://doi.org/10.3390/children12070920 - 11 Jul 2025
Viewed by 455
Abstract
Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM [...] Read more.
Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM cases was conducted. An ultrasound scan was conducted at term between 37 and 40 weeks and amniotic fluid volume (AFV) was assessed by measuring the amniotic fluid index (AFI) and the single deepest pocket (SDP). Maternal demographics and obstetric and perinatal outcomes were evaluated after delivery. We performed comparisons between groups with normal AFV and polyhydramnios (AFI ≥ 24 cm or SDP ≥ 8 cm), and between groups with normal and increased AFV (AFI or SDP ≥ 75th centile). A multivariate logistic regression analysis was performed to study association between AVF measurements and adverse maternal and perinatal outcomes. Results: We found that women with GDM and polyhydramnios at term had a higher risk of maternal (54.3 vs. 27.5%, p < 0.001) and perinatal adverse outcomes (65.7% vs. 46.5%, p < 0.03). The increased AFV group showed a higher risk of fetal overgrowth (LGA: 21.4% vs. 8.2%, p < 0.001 and macrosomia: 19.8% vs. 5.4%, p < 0.001, respectively) and a lesser risk of delivering an SGA fetus (6.3% vs. 13.6%, respectively). Both AFI and SDP showed a significant correlation with newborn weight (r = 0.27; p < 0.001 and r = 0.28; p < 0.001, respectively) and newborn centile (r = 0.26; p < 0.001 and r = 0.26 for both). Subsequent to conducting a multivariate logistic regression analysis adjusted for pregestational BMI, nulliparity, and insulin treatment, both AFI and SDP were significantly associated with perinatal complications, but AFI showed a stronger association with fetal overgrowth (aOR 1.11; p = 0.004 for a LGA fetus and aOR 1.12; p = 0.002 for macrosomia) and with lower risk of delivering an SGA fetus (aOR 0.89; p = 0.009) or IUGR fetus (aOR 0.86; p = 0.03). ROC analysis showed a poor diagnostic performance of both AFI and SDP for identifying macrosomia (AUC 0.68 for AFI, and 0.65 for SDP). Conclusions: Detection of polyhydramnios at term, whether using AFI or SDP, identifies a subgroup of women with gestational diabetes with higher risks of obstetric and perinatal complications. Cases with increased AFV (AFI ≥ 18 cm or SDP ≥ 6.5 cm) are also associated with an increased risk of fetal overgrowth and may require more intensive monitoring for management and optimal delivery timing, with the aim of improve perinatal outcomes. Full article
(This article belongs to the Special Issue Advances in Prenatal Diagnosis and Their Impact on Neonatal Outcomes)
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